Chung Yoonyoung, So Keumyoung, Kim Eunyoung, Kim Seokwon, Jeon Yonghyun
Department of Anatomy, School of Medicine, Chosun University, Gwangju, South Korea.
Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju, South Korea.
Ann Anat. 2015 Jul;200:66-72. doi: 10.1016/j.aanat.2015.02.003. Epub 2015 Feb 25.
Chronic prenatal hypoxia is considered to cause perinatal brain injury. It can result in neurological disorders such as cerebral palsy or learning disabilities. These neurological problems are related to chronic placental insufficiency (CPI), which leads to chronic hypoxemia and hypoglycemia. The effects of hypoxia on neurogenesis during development have been a matter of controversy. We therefore investigated the effect of chronic prenatal hypoxia in the brain of the fetal guinea pig using the guinea pig CPI model. Chronic placental insufficiency was induced by unilateral uterine artery ligation at 30-32 days of gestation (dg: with term defined as ∼67dg). At 50 and 60dg, fetuses were sacrificed and assigned to either the growth-restricted (GR) or control (no ligation) group. Immunohistochemistry was performed with HIF-1α, PCNA, NeuN and BDNF antibodies in the cerebral cortex and dentate gyrus. The number of NeuN-IR and BDNF-IR cells was lesser in GR fetuses than in controls in the cerebral cortex and dentate gyrus at 60dg (p<0.05). The growth of the developing brain is dependent upon the availability of growth factors such as BDNF. The reduction in the number of neuronal cells observed in our GR group was associated with the observed reduction in BDNF protein found at 60dg. There was no significant difference between control and GR fetuses in the densities of PCNA-IR cells in the subventricular zone and subgranular zone at 50 and 60dg. These findings suggest that the survival of neurons in the cerebral cortex is decreased by chronic prenatal hypoxia at 60dg.
慢性产前缺氧被认为会导致围产期脑损伤。它可导致神经障碍，如脑瘫或学习障碍。这些神经问题与慢性胎盘功能不全（CPI）有关，慢性胎盘功能不全可导致慢性低氧血症和低血糖症。缺氧对发育过程中神经发生的影响一直存在争议。因此，我们使用豚鼠慢性胎盘功能不全模型，研究了慢性产前缺氧对豚鼠胎儿大脑的影响。在妊娠30 - 32天（dg：足月定义为约67dg）时，通过单侧子宫动脉结扎诱导慢性胎盘功能不全。在50和60dg时，处死胎儿并将其分为生长受限（GR）组或对照组（未结扎）。在大脑皮层和齿状回中，用HIF - 1α、PCNA、NeuN和BDNF抗体进行免疫组织化学检测。在60dg时，GR组胎儿大脑皮层和齿状回中NeuN免疫反应（NeuN - IR）和BDNF免疫反应（BDNF - IR）细胞的数量少于对照组（p<0.05）。发育中大脑的生长依赖于BDNF等生长因子的可用性。我们的GR组中观察到的神经元细胞数量减少与60dg时观察到的BDNF蛋白减少有关。在50和60dg时，对照组和GR组胎儿脑室下区和颗粒下区PCNA - IR细胞密度无显著差异。这些发现表明，60dg时慢性产前缺氧会降低大脑皮层中神经元的存活率。
